Efficacy of Riluzole in Hereditary Cerebellar Ataxia

NCT ID: NCT01104649

Last Updated: 2015-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2014-03-31

Brief Summary

The hereditary cerebellar ataxias include diverse neurodegenerative disorders. Hereditary ataxias can be divided into autosomal dominant ataxias (ADCAs), autosomal recessive ataxias (ARCAs), X-linked, and mitochondrial ataxias on the basis of mode of inheritance. The key feature in all these disorders is ataxia typically characterised by poor balance, hand incoordination, postural or kinetic tremor, dysarthria and dysphagia.

To date no treatment has been shown to slow progression of the disease and symptomatic therapies are limited to few options that are partially effective.

Purkinje cells project inhibitory signals to the deep cerebellar nuclei(DCN) which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement, while uncontrolled spontaneous firing of DCN neurons may underlay cerebellar ataxia. Recent studies have demonstrated that small-conductance calcium-activated potassium (SK) channels inhibitor are able to increase DCN firing rate. Since SK channels are critical regulators of DCN firing rate, SK openers such as the drug riluzole may reduce neuronal hyperexcitability and thereby be useful in the therapy of cerebellar ataxia.

On this base the investigators published a pilot study in patients with chronic cerebellar ataxia (Ristori et al., Neurology 2010) investigating safety and efficacy of riluzole or placebo administration for 8 weeks. The results demonstrated a significative improvement in International Cooperative Ataxia Rating Scale (ICARS) global score after four weeks and after 8 weeks in the riluzole arm.

The present protocol is aimed at verifying the safety and efficacy of riluzole administration for a longer period, in a larger sample size of patients, with more stringent diagnostic criteria (hereditary cerebellar ataxia), respect to the above pilot study. Sixty patients will be enrolled in a double-blind, placebo-controlled trial. By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 12 months. Treatment effects will be assessed by comparing the Scale for the Assessment and Rating of Ataxia (SARA) before treatment and during therapy at months 3 and 12.

Conditions

Cerebellar Ataxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Riluzole

Riluzole 50 mg is administered orally every 12 hours for 12 months (a 2:1 ratio for SCA/FA in the stratified randomization procedure)

Group Type: EXPERIMENTAL

riluzole

Intervention Type: DRUG

Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Placebo comparator

Placebo is administered orally every 12 hours for 12 months (a 2:1 ratio for SCA/FA in the stratified randomization procedure)

Group Type: PLACEBO_COMPARATOR

Placebo comparator

Intervention Type: DRUG

Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Interventions

riluzole

Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Intervention Type: DRUG

Placebo comparator

Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Intervention Type: DRUG

Other Intervention Names

Rilutek; Placebo

Eligibility Criteria

Inclusion Criteria

• Patients with genetically confirmed diagnosis of hereditary cerebellar ataxia

Exclusion Criteria

• Concomitant experimental therapy for ataxia
• Serious systemic illnesses
• Pregnancy

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agenzia Italiana del Farmaco

OTHER_GOV

Sponsor Role: collaborator

S. Andrea Hospital

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Ristori

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Silvia Romano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome

Locations

Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome

Rome, , Italy

Countries

Italy

References

Ristori G, Romano S, Visconti A, Cannoni S, Spadaro M, Frontali M, Pontieri FE, Vanacore N, Salvetti M. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010 Mar 9;74(10):839-45. doi: 10.1212/WNL.0b013e3181d31e23.

Reference Type: BACKGROUND

PMID: 20211908 (View on PubMed)

Romano S, Coarelli G, Marcotulli C, Leonardi L, Piccolo F, Spadaro M, Frontali M, Ferraldeschi M, Vulpiani MC, Ponzelli F, Salvetti M, Orzi F, Petrucci A, Vanacore N, Casali C, Ristori G. Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015 Oct;14(10):985-91. doi: 10.1016/S1474-4422(15)00201-X. Epub 2015 Aug 25.

Reference Type: DERIVED

PMID: 26321318 (View on PubMed)

Other Identifiers

FARM7KAJM7

Identifier Type: -

Identifier Source: org_study_id